NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) is seeking applications aiming to develop new translational infrastructure/resources to increase the transparency, reproducibility and translatability of animal model preclinical efficacy studies. This FOA solicits Cooperative Agreement (U54) applications to establish a multi-component Alzheimer’s Disease Translational Center for Disease Model Resources (ADTC-DMR). The Center will focus on the development and characterization of transgenic (Tg) and other animal models of AD; discovery and validation of translatable biomarkers, development of standardized methods for preclinical efficacy testing and, definitive efficacy testing of candidate therapeutics using best practices for rigorous study design. Central to this initiative is rapid dissemination of animal models to all qualified researchers for their use in preclinical therapy and transparent reporting of research methodology and preclinical efficacy testing findings. To achieve these goals the Center will need to bring together experts in genomic sciences, computational biology, experts in disease biology, animal model development, neuropathology, electrophysiology, pharmacology, biostatistics and clinical science.

Background

Alzheimer’s disease (AD) is the leading cause of dementia in the elderly affecting greater than 35 million worldwide. In the United States (US) it is estimated that over 5 million people are currently diagnosed with AD, the prevalence of which is predicted to rise to more than 15 million by 2050. It is estimated that the disease currently costs the US healthcare system approximately $200 billion per year. Despite this already large and escalating public health crisis, available treatments are limited to those that produce a modest relief of symptoms. Delaying symptom onset by 5 years could reduce disease prevalence by as much as 50%; this would significantly reduce the human burden and health care costs associated with the disease. Therefore, effective therapies that prevent AD or slow its progression are urgently needed. However, despite significant advances in understanding the neurobiology of AD, the development of effective AD therapies has been challenging, as is evidenced by the extremely high attrition rate for AD treatments with 98% of therapies failing in Phase III.

While there are numerous potential explanations as to why these clinical trials may have failed, one of the major reasons given to account for the high failure rate of AD drugs is the poor predictive power of preclinical efficacy studies performed in AD transgenic (Tg) mouse models. For example, of more than 300 therapeutic agents reported in leading scientific journals to ameliorate pathology and/or cognitive deficits in AD Tg mouse models, none has exhibited significant clinical benefit when tested in large human clinical trials. This problem is not unique to the AD field but affects therapy development for many CNS diseases and disorders

Transgenic animal models have contributed significantly to our understanding of the underlying pathogenic mechanisms of Alzheimer s disease (AD). However, the poor translation of preclinical efficacy from Tg models to patients has led the field to question the validity of the Tg models as representative of the human disease. The lack of predictive validity of the existing mouse models may be dependent on a narrow genetic understanding of AD that has limited the existing models to early-onset AD (EOAD). However EOAD represents only a fraction of AD cases. To date, most of the clinical trials have been done in late-onset AD (LOAD), which represents the majority of AD patients. Therefore, a good strategy for improving the validity of the AD Tg models would be to construct new models using a combination of the recently identified low-risk alleles seen in the majority of LOAD patients. Construction, characterization and deployment of these LOAD models may be expected to improve the predictive power of preclinical efficacy studies.

Another limitation of the existing AD Tg models is that they have not been longitudinally characterized using biomarkers consistent with human disease progression. Recent advances, in biomarker development, made through the Alzheimer’s Disease Neuroimaging Initiative (ADNI) have led to a new clinical perspective of AD as a continuum from pre-clinical pathophysiology to frank clinical dementia. However, contrary to what has been achieved in recent years through ADNI, there has been no systematic evaluation of biomarkers across AD animal models. The development of translatable biomarkers in AD animal models would enable the clinico-pathological staging of an AD-like disease progression corresponding to the currently understood trajectory of human disease. This would be useful in selecting subpopulations of Tg animals modeling specific stages of AD and provide a better translational model for accurately assessing efficacy of candidate therapeutics.

Methodological flaws in the conduct of efficacy studies performed in AD Tg models have contributed to their poor predictive validity. This dearth of best practice standards has led to inadequate data and incorrect conclusions about efficacy. Therefore, if we are to improve the translational validity of AD animal models rigorous best practice and study design guidelines should be developed and adopted by researchers. The best practice guidelines should include a core set of research parameters used when designing studies and reporting results. In addition, best practice guidelines should include a report of the full details of target assay methods and detailed information on the animal model used, including genetic background and transgene copy number.

The translational validity of AD animal models has been limited by legal restrictions that prevent their general use by scientists engaged in therapy development activities. The lack of sharing of AD models restricts the field in that reproducibility is limited when different proprietary models are used by each therapy development program. It is therefore imperative that the next generation of AD Tg models be made readily available to all researchers (academic and industry) engaged in preclinical drug development.

The overarching objective of this initiative is to develop new translational resources and capabilities aimed at bridging the preclinical to clinical development gap posed by the poor reproducibility and translatability of AD animal model efficacy studies. Specifically, this FOA will provide support for: 1) creating the next generation of AD animal models; 2) ensuring the maximal and rapid availability of new models to all researchers (academic and industry) engaged in AD drug development; 3) characterizing and clinico-pathological staging of existing and newly created AD animal models using translatable biomarkers; 4) developing translatable, pharmacodynamics (i.e., target engagement) biomarkers for well validated therapeutic targets; 5) developing and deploying reproducibility strategies such as establishing and implementing guidelines for standardized best practices for the rigorous preclinical testing of AD candidate therapeutics in AD animal models; 6) testing AD candidate therapeutics in AD animal models using standardized best practices; 7) establishing a publically available database housing data generated by the Center. In addition, this initiative will promote the rapid dissemination of animal models to all qualified researchers for their use in preclinical therapy and the transparent reporting of preclinical efficacy testing findings. To achieve these goals the Center will need to bring together experts in genomic sciences, computational biologists, experts in disease biology and animal model development, neuropathologists, electrophysiologists, pharmacologists, biostatisticians and clinicians.

Specific Areas of Research Interest include but are not limited to:

• Creating the next generation of AD models (e.g., mice, rats) to be used in pre-clinical applications such as efficacy-testing, safety and toxicity. New models will be created under intellectual property conditions which ensure their maximal and rapid availability to all researchers (academic and industry) engaged in AD drug development;
• Creating new models of LOAD based on newly identified LOAD risk genes (CLU, CR1, CD33, TREM2, BIN1, etc.) and other genetic variants associated with LOAD as they become available;
• Applying genome manipulation strategies, such as CRISPR/Cas9, Talen and Zinc-finger to introduce relevant variants into animal models;
• Introducing humanized forms of novel therapeutic targets discovered and validated through systems biology approaches (e.g., Accelerated Medicines Program-Alzheimer's Disease or AMP-AD projects);
• Using translational bioinformatics to acquire and analyze relevant human data (genomic, other omic , environmental exposure, network models etc.) from publicly accessible databases to inform the design of the next generation animal models;
• Conducting comprehensive biomarker analysis centered on high-throughput genomic and gene expression platforms as well as other omics data collected in humans and AD animal models. Cross-validation of animal model end-points with clinical measures in humans will be critical;
• Developing translatable small animal imaging modalities (PET, vMRI, fMRI, MRS, etc) to aid the phenotyping and staging of the new and existing animal models;
• Extensive characterization and clinico-pathological staging of existing AD Tg (including mutant APP, APPXPS1/2 and Tau Tg mice) and newly created AD animal models of LOAD with the corresponding stages of clinical disease using translatable biomarkers;
• Identification and validation of translatable pharmacodynamic (i.e., target engagement) biomarkers using "omics data (RNAseq, epigenomic profiling, proteomic, metabolomic) collected in humans and AD animal models;
• Developing and implementing reproducibility strategies including guidelines for standardized best practices for the rigorous preclinical testing of AD candidate therapeutics;
• Standardizing protocols for data acquisition and data analysis across AD animal models and humans;
• Conducting preclinical efficacy testing of candidate AD therapeutics in AD models using standardized best practices, data acquisition and analysis protocols.;
• Developing and implementing methods for formal failure analyses of preclinical efficacy studies;
• Developing strategies for rapid, open-access dissemination of data, and methodology and, for rapid distribution of animal models for their use in therapy development.

The Center should consist of the following units:

• Administrative/ Coordination Core: will manage and coordinate Center research and other activities. In addition, the Unit will have oversight for the sharing of animal models, methods and data both within the center and with the external scientific community.
• Disease Model Development and Phenotyping Project: will be responsible for development of new models and the characterization/staging of new and existing animal models to align them with various clinico-pathologic features of AD. The models will be comprehensively staged vis a vis various human AD features/traits; using various omic platforms. New and existing models will be extensively characterized and clinico-pathologically staged.
• Bioinformatics and Data Management Core: will be responsible for the acquisition, integration and analyses of data acquired from external databases (i.e., ADSP, ADGC, MGI and ADNI) and, data and methods generated by the Center. This unit will develop standardizing protocols for data acquisition and data analysis across AD animal models and humans and, methods for formal failure analyses as a routine approach to understanding why a candidate therapeutic has failed to show preclinical efficacy. This unit will also be responsible for creating and maintaining a publically available database housing data generated by the Center.
• Preclinical Testing Core: will be responsible for adopting and implementing rigorous best practices for preclinical testing of candidate therapies and, testing candidate AD therapies in AD animal models. In addition, this unit will be responsible for developing methods for efficacy testing, preference should be given to PK/PD, biochemical and physiological endpoints, cognitive and behavioral tests as measures of efficacy are discouraged. It is expected that efficacy testing will be conducted in appropriately staged models using human disease mechanism based outcomes and disease-relevant imaging/fluid biomarkers/omics. Emphasis should be placed on using translatable biomarkers that inform the level of target engagement as endpoints to determine the widest possible therapeutic window that will support testing a full dose range in humans. Candidate therapeutics will be selected by the Steering Committee.

Steering Committee: The Center should have a Steering Committee. It will serve as the operational governing board. The Steering Committee should include: the PD(s)/PI(s), Unit leads, the NIH

Project Scientist (voting), the NIH Program Official (ex officio) and external scientists (s) (if required). Among other functions, the Steering Committee will have primary responsibility for finalizing standard procedures and protocols, holding regular teleconferences, reviewing project proposals from the extramural community (academia/biotech/industry) to test candidate therapies in AD animal models, deciding on new projects and developing a prioritized portfolio of therapeutic targets and drug candidates for testing.

External Advisory Board: The Center should have external advisory board organized from non-conflicted experts outside of the Center to guide the center leadership in assessing the Center's progress in achieving the yearly milestones, assessing new scientific opportunities as they are presented and evaluating the effectiveness of interaction among Cores and Center participants. The external advisory board will advise the steering committee on different aspects of the center's function including prioritization of projects, changes in direction or approach, sharing of animal models and data, problem identification and resolution.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Lorenzo M. Refolo, Ph.D
Telephone: 301-594-7576
Fax: 301-496-1494
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (Use for Admin/Coordination Core)	6
Core (Use for Bioinformatics and Data Management Core and Preclinical Testing Core)	6
Project (Use for Disease Model Development and Phenotyping Project)	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required, one
• Admin/Coordination Core: required, one
• Disease Model Development and Phenotyping Project: required, one
• Bioinformatics and Data Management Core: required, one
• Preclinical Testing Core: required, one

When preparing your application in ASSIST, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Other Attachments: The following should be submitted as an attachment in the form of a pdf.

Center organization: A diagram should be made with the organizational structure, leadership and interactions between Units, the Steering Committee and External Advisory Board. This should reflect major decision points and demonstrate collaborative nature of the center. Submit as PDF entitled Center Organization.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: State concisely the goals of the Center and summarize the expected outcome(s), including the impact that the Center will have on Alzheimer's disease research, specifically the impact on preclinical and clinical therapy development, as well as potential clinical impact for the patients. These Aims should be overarching and at a high level and distinct from the aims of the individual units. Refer to the Center Organization pdf diagram requested above. 

Research Strategy: The Center Overview should be presented in a concise overall vision and plan for the proposed Center. Refer to the Center Organization pdf diagram requested above.  This section should describe the framework for the Center, overall experimental strategy and how it will address the objectives of the program. Describe the synergy to be achieved by the Center and how the Bioinformatics and Preclinical Testing units will integrate and inform the Disease Modeling and Phenotyping Unit. Describe how the cutting-edge science emanating from the units will help design and create advanced and predictive AD animal models. Describe how this research will have the potential for assisting in the creation of a preclinical pipeline of therapies that can be moved forward into clinical research and practice.

Additional items to be addressed:

i. Center Organization: The Overall description of the Center should explain: (1) how the components of the Center, including key personnel, will interact; (2) why each component is essential for addressing the overall goal of the Center. There should be bi-directional exchange between the Translational Biomarkers Unit and Preclinical Testing Unit with human clinical studies (including ongoing clinical trials). There should be bi-directional exchange between the Disease Modeling Unit and all other components of the Center.

ii. Milestones and Timeline: The Overall Description of the Center performance and timeline objectives should include: A clear description of all interim objectives to be achieved during the course of the project; detailed quantitative criteria by which milestone achievement will be assessed; and a detailed timeline for the anticipated attainment of each milestone and the overall goal(s).

Letters of Support: An institution applying for an Alzheimer's Translational Center for Disease Model Resources should demonstrate a commitment to the center success. Letter(s) of support from senior administration officials or other institutional officials from the PD(s)/PI(s)' institution(s) should be provided. The letter(s) should describe the level of institutional support for the Center including any leveraged funding or resources that may be provided by the institution(s). All letters of the support for the Overall Unit should be uploaded as a single attachment

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Admin/Coordination Core Head and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe concisely the plans of the proposed Coordination Core leadership and explain the Unit Head's specific roles and responsibilities in the management of the Center. The Coordination Core will conduct oversight for the sharing of animal models, methods and data both within the center and with the external scientific community. Refer to the Center Organization pdf diagram attached in the Overall component. 

Research Strategy: The Coordination Core will provide multidisciplinary scientific leadership for the research center by PDs/PIs, who will have expertise in a particular area of research activities. This unit will effectively coordinate interactions and collaborations of the units and investigators as well as coordinate activities with the NIH Program official. The application should clearly define the management plan for the proposed project, and how it will support achievement of the proposed goals and milestones. The application should also describe the plans for evaluation of progress across the Center and communication strategies to manage and track progress of the multiple units and sharing of disease model resources and data.

Describe Steering Committee. Include plans to convene this group. The committee should include: the PD(s)/PI(s), unit heads, the NIH Project Scientist, NIH Program Official (ex officio) and if necessary external scientists. This committee will make the following key decisions: selection of genetic variants for incorporation into new AD models, selection of candidate biomarkers to be used for characterization of new and currently available AD models, selection of biomarkers of target engagement, selection of validated therapeutic targets, selection of projects for testing candidate therapeutics in AD models, creation of a portfolio of therapeutic candidates to be tested in AD models.

Describe interactions with the Steering Committee in selection and effective prioritization of therapeutic targets and therapeutic candidates.

Describe External Advisory Board. Include plans to appoint and convene this group of up to five members, from outside the Center, at least two times per year and to document its findings and recommendations as well as the Center's changes in direction or approaches made in response. Potential new members should not be solicited or identified in the application.

The Coordination Core should coordinate participation in Center program evaluation activities, including progress towards achieving milestones and evaluating the effectiveness of interaction among units and other Center participants.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Core.'

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Bioinformatics and Data Management Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Bioinformatics and Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Bioinformatics and Data Management Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s): (Bioinformatics and Data Management Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile: (Bioinformatics and Data Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Bioinformatics and Data Management Core Head and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget: (Bioinformatics and Data Management Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan: (Bioinformatics and Data Management Core)

Specific Aims:  Describe concisely the plans of the proposed Unit, specifically its role in creation of precision AD animal models. Describe concisely the specific aims of the Unit and explain how the Unit will interact with the other units of the Center. Describe plans to create and manage a publically available database housing data generated by the Center.

Research Strategy: Indicate how the Core will collect, analyze and integrate sequence and genotype data from outside the Center (e.g., by interfacing with existing NIH and NIA infrastructure: the ADSP, NIA CGAD, ADGC, ADNI, AMP-AD, etc). Describe the strategies, methodologies and computational analyses to be performed. Describe how the Core will prioritize LOAD risk alleles for incorporation into AD animal models, as well as any strategy for the incorporation of combinations of low risk alleles. Indicate how the Core will use current bioinformatics technologies to analyze animal data (e.g., gene expression profiling, proteomic, immunohistochemical, metabolomic, morphological, imaging data, biochemical analysis, etc) to identify and validate translatable biomarkers that can assist in clinico-pathological staging of an AD-like disease progression in AD animal models. Describe the strategies, methodologies and analyses to be performed by the Unit to integrate existing human bioinformatics data (e.g., by interfacing with existing NIA and NIH infrastructure i.e., ADNI) for the purpose of cross validating biomarkers obtained from animal bioinformatics. Indicate how the Core will develop a data base for rapid and open-access dissemination of data and methodology generated by the Center.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Bioinformatics and Data Management Core

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide

PHS 398 Cumulative Inclusion Enrollment Report (Bioinformatics and Data Management Core

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide

When preparing your application in ASSIST, use Component Type Core'

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover: (Preclinical Testing Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement: (Preclinical Testing Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Preclinical Testing Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s): (Preclinical Testing Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile:(Preclinical Testing Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Pre-clinical Testing Core Head and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget: (Preclinical Testing Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan: (Preclinical Testing Core)

Specific Aims:  Describe concisely the plans of the proposed Core, specifically its role in testing candidate therapies in precision AD animal models. Describe concisely the specific aims of the Core and explain how the Core will interact with the other components of the Center.

Research Strategy:  Describe how the core investigators will develop and implement standardized best practices for the rigorous preclinical testing of AD candidate therapeutics, including a core set of reporting standards. Describe the experimental approaches for testing candidate therapeutic agents, including the use of translatable pharmacodynamic (PD) biomarkers in evaluating therapeutic agents and, pharmacodynamic (PD)/pharmacokinetic (PK) approaches that may be required as part of evaluation of agents. Of special interest is the development of phenotypic screens that can be used to assess the ability of one or multiple compounds to normalize the activity of entire networks as therapeutic targets. Describe approaches to formal failure analysis of preclinical trials.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide

Planned Enrollment Report (Preclinical Testing Core

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide

PHS 398 Cumulative Inclusion Enrollment Report (Preclinical Testing Core

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Project'

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover: (Disease Model Development and Phenotyping Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement: (Disease Model Development and Phenotyping Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information: (Disease Model Development and Phenotyping Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s): (Disease Model Development and Phenotyping Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile:(Disease Model Development and Phenotyping Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Disease Model Development Director and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget: (Disease Model Development and Phenotyping Project)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan:(Disease Model Development and Phenotyping Project)

Specific Aims:  Describe concisely the plans of the proposed Project, specifically its role in creation of precision AD animal models. Describe concisely the specific aims of the Project and explain how the component will interact with the other components of the Center. Include in the Specific Aims a target of at least 3 next generation AD model projects, including plans to incorporate combinations of multiple low-risk alleles to better model LOAD. Briefly describe plans for the clinico-pathological staging of at least 3 next generation and 3 current AD animal models.

Research Strategy: Describe each next generation AD model project, including its testable hypothesis, and a rationale for prioritizing alleles or allele combinations, as well as how each project will improve the translational validity of AD models.  Demonstrate use of new technologies, including in vivo genome editing technologies. Indicate how the Project will develop and characterize translational biomarkers for the purpose of longitudinally characterizing AD animal models. Specifically discuss how the Project will use current technologies (e.g., gene expression profiling, proteomic, immunohistochemical, metabolomic, morphological, imaging data, biochemical analysis, etc) to conduct a biomarker discovery campaign using samples from animal sources. Indicate how new models will be phenotypically characterized, including any new phenotyping technologies. Discuss how the Project will cross validate animal biomarker endpoints with human data. Indicate how the Project will develop and validate translatable, pharmacodynamic biomarkers that can assess target engagement.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Disease Model Development and Phenotyping Project)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide

PHS 398 Cumulative Inclusion Enrollment Report (Disease Model Development and Phenotyping Project)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute on Aging (NIA), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the {National Institute on Aging Scientific Review Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed).

What is the likelihood that the project will achieve the overarching goals of the Alzheimer's Disease Translational Center to create, characterize and, rapidly disseminate to all qualified researchers the next generation of AD animal models? What is the likelihood that the project will have a positive impact on the direction of Alzheimer's disease research, specifically its impact on preclinical and clinical therapy development and potential avenues for the treatment and prevention of the disease?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on therapy development for Alzheimer's disease, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed.)

• Does the application have a single clearly defined and scientifically justified theme?
• Does the application adequately explain the following:
  • The program as a whole?
  • Significance of the overall program goals?
  • Scientific gains and synergy achieved by combining the components (project and cores) into a multi-project program beyond the gains achievable if each project were pursued independently?
• Does the application adequately describe the overall experimental strategy of the Center and does the experimental strategy address the objectives of the Center?
• Are the overall program goals significant and focused on studies that increase knowledge needed to advance the translational activities of the Center?
• How well does the overall program incorporate innovative concepts and approaches?
• Is the program as a whole cohesive and do the Research Project and Cores relate to a single common theme demonstrating cohesion, multidisciplinary interactions, coordination, and synergy?
• Reviewers will comment on whether the following Resource Sharing Plans are reasonable: 1) Data Sharing Plan; 2) Sharing of Model Organisms; 3) Genomic Data Sharing Plan

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a core or project that by its nature is not innovative may be essential to advance a field.

Does the Center address an important problem or a critical barrier to progress in the field? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? To what extent do key personnel in the center have expertise in genomic sciences, computational biology, disease biology, animal-model development, neuropathology, electrophysiology, pharmacology, pre-clinical therapy development, biostatistics and clinical research? To what extent does the Center Program Director/Principal Investigator (PD/PI) or contact PD/PI for applications with multiple PDs/PIs have expertise in disease-animal modeling, preclinical and/or clinical research?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? To what extent is the proposed science "cutting edge"? Is the science sufficiently innovative to design and create advanced and predictive AD animal models?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? How well do the Center cores and project interact to achieve synergy? How clearly are the milestones and timeline established? To what extent is the timeline feasible given the organization and goals of the Center?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? How well do the Institutional resources support the particular needs of Alzheimer's preclinical and clinical drug development?

As applicable for the Centers proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Significance

Does the Administrative Core address an important problem or a critical barrier to progress in the field? If the aims of the Core are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

How well do the plans for the proposed activities within the framework of the Center as a whole position it appropriately to coordinate the center's activities? To what extent is the planned oversight for the sharing of animal models, methods and data within the Center and with the external scientific community appropriate to the needs of the center and the community? How well does the core synergize the interactions, approaches and collaborations with the Center?

To what extent do the plans for measuring progress across the Center including achievement of the proposed milestones convey a comprehensive assessment of the center's functioning? Are plans to convene a Steering Committee presented and are the activities of the Steering Committee clearly described? Are the plans to appoint and convene an External Advisory Board presented and are the activities of the External Advisory Board clearly described?

Investigators

Are the core leadership, collaborators, and other researchers well suited to the Core? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the core is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the core challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are plans in place for collaboration and cooperation with the other Center investigators and other key external scientists that will augment the likelihood of accomplishing the Center's goals and objectives?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Are the mechanisms for the evaluation of progress across the Center and communication strategies to manage and track progress sound and robust? What is the likely effectiveness of the utilization of the Steering Committee and External Advisory Board in conducting oversight and monitoring of different aspects of the center's function, including prioritization of LOAD alleles for incorporation into AD animal models, therapeutic targets and drug candidates, as well as in problem identification and resolution?

Are plans for the following Administrative/Coordinating Core functions adequate:

• monitoring timelines for achieving milestones;
• ensuring appropriate prioritization of activities;
• providing and maintaining a publically available data base;
• sharing data and AD models within the Center and with external researchers?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the core benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Significance

Does the Bioinformatics and Data Management Core address an important problem or a critical barrier to progress in the field? If the aims of the Core are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

How well does the Core meet the overall needs of the Center? Are the interactions of the Core with other units of the Center well described? How well-positioned is the core to collaborate with existing NIH and NIA infrastructure/databases: the ADSP, NIA CGAD, ADGC, ADNI, AMP-AD, etc.? Is there a clear plan for construction and management of the Center data base and are clear plans delineated for the sharing of data within the Center?

Investigators

Are the core leadership, collaborators, and other researchers well suited to the Core? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the core is collaborative do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Have the core leadership and other key personnel demonstrated a record of directing informatics and data management activities related to Bioinformatics and Data Management Core?

Innovation

Does the Core challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Is a clear plan for active participation in analysis of the animal model discoveries for validation purposes as well as refinement of the model provided? Does the Core have full access to high quality genetic/omics data sufficient to formulate a strategy necessary to develop next generation AD models (particularly of LOAD)? To what extent are the strategies, methodologies and analyses proposed for integrating existing human bioinformatics data able to maximize the value of the integrated set? How well do the strategies, methodologies and analyses proposed for acquisition of animal bioinformatics position the center to incorporate animal bioinformatics into advancing Alzheimer's animal models?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Core? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Is there a clear plan to prioritize LOAD risk alleles, including combinations of low risk alleles, for incorporation into AD animal models? Is there a clear plan to use current bioinformatics technologies to conduct analysis of animal data (e.g., gene expression profiling, proteomic, immunohistochemical, metabolomic, morphological, imaging data, biochemical analysis, etc) for the purpose of identifying and validating translatable biomarkers, including pharmacodynamic (PD) biomarkers?

Are the plans for developing and maintaining a Center database adequate? Is there a clear plan for rapid, open dissemination of data and bioinformatics methodology generated by the Center? Is the plan to develop methods to track experiments, document workflows and link this information to the Center database adequate?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the core benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Significance

Does the Preclinical Testing Core address an important problem or a critical barrier to progress in the field? If the aims of the Core are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the interactions of the Core with other units of the Center well described and appropriate? Does the Core have the potential for providing high quality efficacy data that has improved translational value? To what extent will the Core be capable of collaborating with institutional clinical research to facilitate bidirectional translation of data and thereby inform or improve clinical care and improve the usefulness of the AD animal models?

Investigators

Are the core leadership, collaborators, and other researchers well suited to the Core? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)??

Have the core leadership) and other key personnel demonstrated a record of directing preclinical research activities related to Preclinical Testing Core?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Is there a clear and adequate plan for the use of translatable pharmacodynamic (PD) biomarkers in evaluating the efficacy of therapeutic agents? Is there a clear and adequate plan to develop phenotypic screens for the purpose of assessing efficacy of one or multiple agents?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Core? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Is the plan to develop methods to track experiments, document workflows and link this information to the Center database adequate? Are the plans to align pre-clinical and clinical study designs appropriate to the need? How comprehensive are the plans to utilize dosing, pharmacokinetics (PK), pharmacodynamics (PD) and absorption, distribution, metabolism, excretion and toxicity (ADMET) in preclinical efficacy trials? Are the plans to develop and implement standardized best practices for the rigorous preclinical testing of AD candidate therapeutics well-reasoned and appropriate?

Are there strategies for incorporating both biomarkers and functional and translatable endpoints into preclinical efficacy testing of candidate therapeutics? Is there a strategy for using appropriate staged (clinico-pathological) animals to evaluate treatment effects at different stages of disease? Are the approaches to formal failure analysis of preclinical trials well-reasoned and adequate?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the core benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Scored Review Criteria for Disease Modeling and Phenotyping Project

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are plans for interaction with other components of the Center, Coordination Core, Pre-clinical Testing Core and Bioinformatics and Data Management Core well described? Is strong justification/rationale provided for potential therapeutic benefit derived from the use of the proposed AD animal models?

How well will the created animal models be able to recapitulate specific alleles and genomic, proteomic, metabolomic and other biological indicators of AD, particularly LOAD?

Investigators

Are the project leadership, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Have project leadership and other key personnel demonstrated a record of directing research activities related to creating and validating animal models of disease?

Innovation

Does the project challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the project utilize the current advances of genome editing and other cutting-edge technologies?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Are the conceptual framework, testable hypothesis, design, methods and analyses adequately developed, well integrated, well-reasoned and appropriate to the AD modeling research project?

Is the choice of the particular animal species as a model system for AD, particularly LOAD, well-justified? Are the plans for prioritization of LOAD alleles for incorporation into AD animal models well-reasoned and well described and adequate?

Are the plans for the clinico-pathological staging of at least next generation and current AD animal models well described and adequate? Is there a plan to cross validate animal biomarker endpoints with human data? Is the plan well-reasoned? Is there a clear plan for active analysis, validation and refinement of the AD animal models?

Are the overall strategies, methodologies and analyses for conducting a translatable biomarker campaign well-reasoned and appropriate? Is the plan to use biomarkers to stage and phenotypically characterize AD animal models well-reasoned and adequate?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the core benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NIA in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Milestones

Because drug discovery and development are inherently high risk, it is expected that there may be significant attrition as projects progress. Milestones (typically a minimum of one per funding year) will be established by the PD/PI in collaboration with NIA Program Staff at the start of the project and updated as needed. The application must include milestones with quantitative success criteria for each year of funding. Each year the PD/PI must submit milestone progress reports for independent evaluation by NIA Program Staff. The milestone plan is developed at the outset of the project, in collaboration with NIA Program Staff.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below:

The PD(s)/PI(s) will have the primary responsibility for:

• Formation of a Steering Committee which will serve as the operational governing board. The Steering Committee should include: the PD(s)/PI(s), Unit leads, the NIH Project Scientist (voting), the NIH Program Official (ex officio) and external scientists (s) (if required);
• Determining experimental approaches, designing protocols, conducting experiments, and analyzing and interpreting research data for studies funded through this U54.  The PD/PI is ultimately responsible for the project and will make the final decisions regarding all project plans, provided that they can be executed within NIA/NIH-approved budgets and according to NIA/U54 grant and contract policies;
• Leading the project as a whole, and agree to accept close assistance, advice, coordination, and collaborate with the NIA Project Scientist and other awardees;
• They will determine experimental approaches, design protocols, set project milestones and conduct experiments;
• Participating in group activities, including Steering Committee, to share design and analysis techniques and promote comparability across studies wherever possible;
• Ensuring active participation of partner sites and collaborators in group activities, if applicable;
• Implementing Steering Committee recommendations for designing, implementing, evaluating, and disseminating Disease Modeling Projects, as appropriate and feasible;
• Adhering to the general NIA/NIH policies regarding sharing resources, data release, and resource sharing, as well as the specific data and resource-sharing policies proposed in the application, as modified by any negotiation prior to award;
• Adhering to NIA/NIH policies, including those regarding data release, intellectual property, and publications;
• Submitting periodic milestone reports in a standard format, as agreed upon by the Steering Committee;
• Attending and participating in Steering Committee meetings and accepting and implementing the guidelines and procedures, as appropriate;
• Implementing all scientific and policy decisions approved by the NIA/NIH.

NIA staff has substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIA Program Official will be assigned to the project and will be responsible for the normal scientific and programmatic stewardship of the award. The NIA Program Official will be named in the award notice and will be the primary contact with the PI/PD. The Program Official will be responsible for assessing the progress of the project towards accomplishment of milestones, and for recommending the level of continued funding.

An NIA Project Scientist will be assigned to the project with substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice and coordination that is above and beyond the normal stewardship role in awards. The NIA Project Scientist will provide additional expertise that is needed for proper scientific management of the award. This includes assisting the PI/PD in enhancing the project's progress by providing access to various NIH resources, when appropriate, providing technical assistance, advice, and coordination to the project, although the dominant role and responsibilities for the activities funded by the U54 reside with the PI/PD.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop appropriate strategies and tools to develop precision AD animal models.

Steering Committee: The awardees and the NIA Project Scientist will meet as the Center Steering Committee at least one time per year in person and monthly on conference calls as needed to share information on data resources, methodologies, analytical tools, as well as data and preliminary results. The Steering Committee should include: the PD(s)/PI(s), Unit leads, the NIA Project Scientist (voting), the NIH Program Official (ex officio) and external scientists (s) (as required). Key co-investigators and pre- and postdoctoral trainees, especially those who are members of under-represented groups or those from different but related disciplines, in addition to the PD/PIs, are eligible to attend these meetings.

The Steering Committee will:

• Participate in monitoring "day to day" scientific progress of the research project plan, assessing progress of the milestones.
• Review project proposals from the extramural community (academia/biotech/industry) to test candidate therapies in AD animal models, decide on new projects and develop a prioritized portfolio of therapeutic targets and drug candidates for testing
• Convene video or audio teleconferences and yearly meetings to monitor progress on the research project plan and to address issues or activities that impact the project, identify areas of shared interest and potential for collaboration.
• Establish workgroups for specific tasks as needed, which could include representatives from the program and the NIA
• Meet at least annually with the External Advisory Board, or as dictated by the needs of the Project.

External Advisory Board: In consultation with NIA staff, an external board of advisors will be selected, to be comprised of individuals not directly involved in the Center to guide the center leadership in assessing the progress in achieving the yearly milestones, assessing new scientific opportunities as they are presented and evaluating the effectiveness of interaction among units and Center participants.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Lorenzo M. Refolo, Ph.D
National Institute on Aging (NIA)
Telephone: 301-594-7576
Email: [email protected]

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Jillian Morris
National Institute on Aging (NIA)
Telephone: 301-496-8386
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.